A novel factor binding to the glucose response elements of liver pyruvate kinase and fatty acid synthase genes

Jun Ichi Hasegawa, Kiyoshi Osatomi, Ru Feng Wu, Kosaku Uyeda

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Transcription of the Iiver type pyruvate kinase and lipogenesis enzyme genes is induced by high carbohydrate in liver. We have found a novel protein factor in rat liver nuclei that binds to the glucose response element (CACGTG motifs) of the pyruvate kinase gene (Liu, Z., Thompson, K. S., and Towle, H. C. (1993) J. Biol. Chem. 268,12787-12795) and the 'insulin response element' of fatty acid synthase gene. The amounts of this DNA-binding protein, termed 'glucose response element binding protein' (GRBP) in the nuclear extract, were increased in liver by a high carbohydrate diet and decreased by starvation, high fat, and high protein diet. GRBP also occurs in cytosols of liver and is dependent on carbohydrate. Both the nuclear and the cytosolic GRBP showed similar properties, except the former was more resistant to thermal inactivation than the latter. Kinetics of glucose activation of the cytosolic GRBP in a primary culture of hepatocytes indicated that a half- maximum activation was achieved after 6 h, and glucose concentration required for the maximum activation of the GRBP was approximately 12 mM. Dibutyryl- cAMP, okadaic acid, and forskolin inhibited glucose activation of both GRBP and liver pyruvate kinase transcription. These results suggested that GRBP may be a factor that recognizes the glucose response motif site and may be involved in mediating carbohydrate response of the pyruvate kinase gene.

Original languageEnglish (US)
Pages (from-to)1100-1107
Number of pages8
JournalJournal of Biological Chemistry
Volume274
Issue number2
DOIs
StatePublished - Jan 8 1999

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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